Cenicriviroc Mesylate is a dual CCR2/CCR5 antagonist, also inhibits both HIV-1 and HIV-2 with anti-inflammatory and antiinfective activity.

Migration of mouse monocytes in response to carbon tetrachloride (CCL2) is reduced following pre-treatment with Cenicriviroc Mesylate (CVC) at a concentration of 1 μM. Compare to untreated and unstimulated cells, the average fold change in migrating cells is 0.8±0.2 (p>0.05) and 0.7±0.4 (p>0.05) for CCL2-stimulated cells treated with Cenicriviroc Mesylate and unstimulated cells treated with Cenicriviroc Mesylate, respectively [1]. Phenotypic susceptibility testing shows, for the four R5-tropic HIV-2 isolates, a median EC50 for Cenicriviroc Mesylate of 0.39 nM. The dual-tropic and the X4-tropic HIV-2 strains are resistant to Cenicriviroc Mesylate with EC50 at >1000 nM, and Maximum percentages of inhibition at 33% and 4%, respectively [2].

Treatment with Cenicriviroc Mesylate results in a dose-dependent reduction in monocyte/macrophage recruitment, reaching statistical significance at dosages of 20 mg/kg/day or higher. When compared to the vehicle-control group, Cenicriviroc Mesylate administration at dosages of 5 mg twice daily (BID), 20 mg BID, 100 mg BID, and 20 mg once daily (QD) leads to decreases in peritoneal lavage monocyte/macrophage counts of 5.7%, 45.2%, 76.5%, and 26.0%, respectively. The effect of Cenicriviroc Mesylate on reducing monocyte/macrophage recruitment is dose-related and demonstrates a correlation with dosage, showing greater efficacy for twice daily (BID) administration compared to once daily (QD). This increased effectiveness is likely due to the higher plasma concentrations achieved with BID dosing and the compound's short half-life of approximately 2 hours in mice [1].